Urease is a water soluble enzyme used in dialysis to convert urea into ammonium ions and bicarbonate. Oftentimes, urease can be immobilized electrostatically, covalently, or by adsorption on an alumina or silica substrate inside a sorbent cartridge that is designed to be connected to a dialysis system. However, conventional immobilization of urease has been associated with the disadvantages of low loading and leaching of urease that can result in insufficient amounts of urease for dialysis. Moreover, conventional sorbent dialysis systems cannot replenish, i.e., provide additional or specified amounts of urease, to the known sorbent cartridges or dialysis systems. The inability to add urease, and control the amount of urease added, to the sorbent system use can be problematic because the amount of urease required for a particular dialysis session can vary. The amount of urease required for a dialysis session may depend on a number of factors such as patient weight, urea load, dialysis time, etc. resulting in different rates and amounts of urease required per session. Using more or less than the required amount of urease for a particular dialysis session can translate into increased expenditures and waste from unused or overused urease as well as other sorbent materials contained in the sorbent cartridge.
Known sorbent dialysis cartridges and systems further cannot measure the amount of urease used during a particular session or even replenish or add urease back to the sorbent cartridge or system during operation as needed, should a session need additional quantities of urease or should additional urease be needed in the case of faster fluid flow rates through the sorbent cartridge. Sometimes, certain sorbent materials such as alumina and zirconium phosphate can be recharged such that the sorbent material is put back into a condition for use in sorbent based dialysis (see U.S. application Ser. No. 14/261,651). As such, known sorbent systems cannot recharge some or all of the sorbent materials, some of which can be rechargeable components within the sorbent cartridge, without undesirable effects. For example, recharging zirconium phosphate in the same sorbent cartridge in which urease is immobilized on alumina can result in urease, which is bound to an alumina layer, being stripped off the alumina. More generally, recharging certain rechargeable sorbent materials in known sorbent cartridges can sometimes have undesirable effects on other sorbent materials contained inside the same sorbent cartridge. Known systems cannot replenish such urease lost due to recharging of other sorbent materials, or add a specific amount of urease to a sorbent cartridge or sorbent system during operation.
As such, there is a need for systems, methods, components and devices for optimizing use of sorbent materials such as urease within a sorbent cartridge. The need extends to systems that can replenish urease in a sorbent cartridge, and related systems, by either directly adding discrete amounts of urease or by continuously adding urease to the sorbent system by a delivery mechanism. The need includes a sorbent cartridge and related systems in which urease can be added on demand, continuously, and in specified, discrete amounts. The need extends to providing urease at a specified time such as after, before, or during a dialysis session. The need includes providing the urease while the system is operating or off-line. There is also a need for a modular system, such as a system of different sized urease pouches that contain urease of different quantities that can be easily added to a sorbent cartridge and related systems. The need includes adding the desired amounts of urease in a simple and convenient manner and in adjustable amounts. The need includes a sorbent cartridge having a section wherein an adjustable amount of urease can be added. There is also a need for a sorbent cartridge having a section for containing adjustable amounts of urease. The need includes a sorbent cartridge optionally having a section for containing one or more sorbent materials that can be in a fixed amount. In general, the need can be broadly described as dynamically adding urease to sorbent cartridges and related dialysis systems. The need can include adjusting the amount of required urease depending on a measured amount of ammonia detected anywhere in the system or sorbent cartridge.
There is a further need for a closed sorbent cartridge capable of receiving an adjustable amount of urease, on demand. The need includes methods for measuring, refilling, and/or replenishing urease during a dialysis session. The methods and systems require a way for introducing urease in continuous or specified and/or discrete amounts. The methods and systems may involve pre-set amounts of urease or dynamically adjustable amounts of urease. There is also a need for a system capable of replenishing urease that may be stripped out of the sorbent cartridge lost during maintenance or during a dialysis session.